The vaccine confidence index in Japan is one of the lowest worldwide. This study aimed to examine the proportion of COVID-19 vaccine hesitancy in the Japanese population using a larger sample and more robust statistical methods than previously, and to identify factors associated with vaccine hesitancy. We conducted a nationwide, cross-sectional Internet survey on 8–26 February 2021, and calculated the proportion and odds ratios for vaccine hesitancy. Among 23,142 responses analyzed, the proportion of COVID-19 vaccine hesitancy was 11.3% (10.9–11.7%). The proportion was higher among younger respondents and female respondents, and especially among younger female respondents (15.6%) compared with the lowest proportion among older male respondents (4.8%). The most cited reason for not getting vaccinated was concerns about adverse reactions in more than 70% of the respondents. The proportion of COVID-19 vaccine hesitancy in Japan was comparable to that in previous studies overseas, and the proportion among younger respondents was more than double that among older respondents. Factors associated with the hesitancy were female sex, living alone, low socioeconomic status, and presence of severe psychological distress, especially among older respondents. Thus, adequate measures should be taken to ensure that vaccines are delivered to people with these factors.

Objective To investigate the factors associated with serious psychological distress (SPD) during the COVID-19 pandemic in Japan. Design Nationwide cross-sectional study using survey data. Setting Internet survey using sampling weights for national estimates conducted between 25 August and 30 September 2020 in Japan. Exposures Demographics (age, gender), socioeconomic status (income level, employment type, educational attainment, marital status, family composition and caregiving burden); the experience of domestic violence (DV), the state of emergency and fear of and stigma related to COVID-19. Main outcome measures Prevalence of SPD, defined as Kessler 6 Scale score ≥13. Results Among 25 482 respondents, 10.0% met the criteria of SPD. Overall, women (adjusted OR (aOR) 1.59; 95% CI 1.17 to 2.16; p=0.003), ages 15–29 (aOR 2.35 compared with ages 45–59 years; 95% CI 1.64 to 3.38; p<0.001), low-income level (aOR 1.70 compared with intermediate income; 95% CI 1.16 to 2.49; p=0.007), providing caregiving to family members (aOR 5.48; 95% CI 3.51 to 8.56; p<0.001), experiencing DV (aOR 5.72; 95% CI 3.81 to 8.59; p<0.001) and fear of COVID-19 (aOR 1.96; 95% CI 1.55 to 2.48; p<0.001) were associated with SPD. Among women aged 15–29 years, who have a higher risk of suicide during the COVID-19 pandemic in Japan, caregiving, DV, fear of COVID-19 and COVID-19-related stigma were associated with SPD. Conclusions Economic situation, caregiving burden, DV and fear of COVID-19 were independently associated with SPD during the COVID-19 pandemic. Among young women, similar factors, except economic situation, were associated with SPD. Targeted interventions based on age and gender may be more effective in mitigating the negative impact of the COVID-19 pandemic on the population’s mental health.

Glioblastoma is a primary brain tumor associated with a poor prognosis due to its high chemoresistance capacity. Cancer stem cells (CSCs) are one of the mechanisms of chemoresistance. Although therapy targeting CSCs is promising, strategies targeting CSCs remain unsuccessful. Abnormal activation of epidermal growth factor receptors (EGFRs) due to amplification, mutation, or both of the EGFR gene is common in glioblastomas. However, glioblastomas are resistant to EGFR tyrosine kinase inhibitors (EGFR-TKIs), and overcoming resistance is essential. Brexpiprazole is a new, safe serotonin-dopamine activity modulator used for schizophrenia and depression that was recently reported to have anti-CSC activity and function as a chemosensitizer. Here, we examined its chemosensitization effects on osimertinib, a third-generation EGFR-TKI with an excellent safety profile, in glioma stem cells (GSCs), which are CSCs of glioblastoma. Brexpiprazole treatment sensitized GSCs to osimertinib and reduced the expression of survivin, an antiapoptotic factor, and the pharmacological and genetic inhibition of survivin mimicked the effects of brexpiprazole. Moreover, co-treatment of brexpiprazole and osimertinib suppressed tumor growth more efficiently than either drug alone without notable toxicity in vivo. This suggests that the combination of brexpiprazole and osimertinib is a potential therapeutic strategy for glioblastoma by chemosensitizing GSCs through the downregulation of survivin expression.

Background and Objectives: The relationship between social isolation/loneliness and oral health is unclear. This study investigated the association between social isolation/loneliness and tooth loss in older Japanese adults. Research Design and Methods: This was a cross-sectional study of a population-based cohort (the Sukagawa Study); 5,490 cohort study participants aged ≥75 years and who were independent answered a self-administered questionnaire in 2018. Social isolation was defined based on the 6-item Japanese version of the Lubben Social Network Scale. Loneliness was measured by the 3-item Japanese version of the University of California, Los Angeles (UCLA) Loneliness Scale version 3. The primary outcome was tooth loss, defined as having fewer than 20 teeth. The secondary outcomes were decreased toothbrushing frequency and diminished ability to chew food. Prevalence ratios (PRs) were estimated using a modified Poisson regression analysis in 2 models—Model 1, which adjusted for age, gender, smoking status, alcohol consumption, low annual income, and short education period, and Model 2, which added history of depression, history of diabetes mellitus, history of stroke, and cognitive impairment to Model 1. Results: The primary analysis included 5,490 participants. Adjusted PRs of social isolation and loneliness for tooth loss (Model 1) were 0.97 (95% confidence interval [CI] 0.93–1.01) and 1.07 (95% CI 1.02–1.12), respectively; those for decreased toothbrushing frequency were 1.17 (95% CI 0.98– 1.39) and 1.59 (95% CI 1.30–1.93), respectively; and those for chewing difficulty were 1.65 (95% CI 1.12–2.43) and 3.01 (95% CI 2.02–4.51), respectively. The adjusted PRs in Model 2 demonstrated results similar to that of Model 1. Discussion and Implications: Loneliness is associated with tooth loss among older adults, whereas social isolation is not. Our findings can inform plans for policymakers, professionals, and organizations to identify lonely older adults and provide social prescriptions to improve their access to oral health care services.

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